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Zinc Finger Proteins pp 39–46Cite as

Zinc Finger Interactions with Metals and Other Small Molecules

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Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

Abstract

Zinc fingers encompass a wide variety of compact protein domains that are stabilized by a structural zinc ion which minimally interacts with a cysteine-rich coordination sphere. The selectivity for zinc ion binding is governed by coordinating amino acid side chains and by thermodynamic parameters. Since metal coordination spheres in zinc finger proteins are susceptible to chemical attack (principally at thiolates) and because zinc finger proteins have prominent roles in many cellular processes including the regulation of gene expression and signal transduction, an underlying mechanism for a number of cellular dysfunctions is likely to be the disruption of zinc coordination spheres by a variety of metals and other small molecules. For instance, a number of toxicity mechanisms are likely to be the consequence of zinc replacement by xenobiotic metals resulting in changes in polypeptide conformation and the concomitant loss of protein function. Zinc finger disruption could also occur by oxidation and modification of critical cysteine and histidine amino acids in the zinc coordination sphere resulting in zinc release and alteration of conformation. The chemical reactivity of metal coordination spheres of zinc finger proteins are utilized in normal physiological processes by providing regulatory sites for signal transduction via small molecules like nitric oxide and oxygen and their reactive intermediates. In addition, zinc finger proteins and their metal binding sites are promising targets for specific drug design to help ameliorate major diseases.

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Authors and Affiliations

  1. University of Oklahoma College of Medicine, Oklahoma City, Oklahoma, USA

    Jay S. Hanas, Jason L. Larabee & James R. Hocker

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  1. Jay S. Hanas
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  2. Jason L. Larabee
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Correspondence to Jay S. Hanas .

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Editors and Affiliations

  1. Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA

    Shiro Iuchi

  2. Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Natalie Kuldell

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Hanas, J.S., Larabee, J.L., Hocker, J.R. (2005). Zinc Finger Interactions with Metals and Other Small Molecules. In: Iuchi, S., Kuldell, N. (eds) Zinc Finger Proteins. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-27421-9_8

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